Introduction:
Neonatal sepsis is the leading cause of neonatal mortality in the
developing world. There is an increasing incidence of drug resistance
among organisms. We have tried to the sepsis profile in our nursery and
to assess the validity of sepsis screen as a diagnostic tool. We have
also studied the individual parameters of the screen for their strength
as a diagnostic tool. Methods:
This was a prospective study carried out in the SCNU of MY Hospital and
included 200 newborns with suspected sepsis. Sepsis Screen and Blood
Cultures were done in all the babies and the results were analysed. Results: Out of the
200 patients with suspected sepsis, 150 (75%) had a positive sepsis
screen whereas 102 (51%) were culture positive. Sepsis Screen was
positive in 93.1% of total culture positive sepsis and in 56.1% of
culture negative cases too. Thus, the Sensitivity and specificity for
Septic Screen was calculated to be 93.18 and 43.88% repetitively. PPV
was 63.33% and NPV was 86.0 %. Conclusion:
The bacteriological flora has changed over the last 12 years and there
has been a high incidence of resistance to the first live antibiotics
in our Nursery. The sepsis screen has a high negative predictive value
and it is recommended that negative sepsis screen should warrant
discontinuation of the empirical antibiotics to prevent the unnecessary
use and the emergence of drug resistant organisms.

Neonatal sepsis is the leading cause of neonatal mortality. It is
responsible for 13% of all neonatal mortality, and 42% of deaths in the
first week of life [1,2]. The multiple skin punctures and invasive
procedures that preterm newborns commonly undergo increase even more
the risk of infections in this population.

In developing countries, clinically diagnosed sepsis is present in
49–170 per 1000 live births, culture-proven sepsis in 16 per
1000 live births and neonatal meningitis in 0.8–6.1 per 1000
live births[3].

Even though a positive blood culture, is gold standard for diagnosis of
neonatal sepsis the technique is time consuming, demands a proper
laboratory setup and is positive in only 40% cases.

Early treatment with antibiotics is possible with the help of certain
indirect markers such as neutropenia (<1800 cells/mm3),
leucopenia (<5000 cells/mm3), band cells, I/T ratio of >
0.2, Platelet Count of < 150000/cumm micro ESR >15mm in
1st hour and C-reactive protein (CRP) value of >1 mg/L [4,5].
All these investigations are collectively known as sepsis screen and
aids in early diagnosis of neonatal sepsis in absence of negative blood
cultures. This screen has been used for a long time for the diagnosis
of suspected and probable sepsis.

We tried to calculate the sensitivity, specificity positive and
negative predictive value of the sepsis screen to diagnose the proven
sepsis. We also tried to assess the strength of individual parameters
as a diagnostic tool for sepsis.

Materials
and Methods

Place and type of study:
The prospective study was carried out in SNCU (Special Care Newborn
Unit) of M.Y. Hospital, Department of Pediatrics, MGM Medical College,
Indore (M.P.)

Sampling: A
total of 200 newborns, inborn and out born admitted in SNCU of M.Y.
hospital, Indore were taken up for study over a period of 6 months in
2016 from May to October.

Exclusion criteria:
Major congenital anomalies like tracheoesophageal fistula, malrotation
of the gut, lobar agenesis of lungs, congenital heart disease or
anomalies of the CNS were excluded from the study.

Methods:
Following investigations were done in all the cases,Hb, T & D,
Band Cell Count, Thrombocyte count, Immature /Total neutrophil ratio,
CRP, micro ESR and blood culture. The sepsis screen comprised of Total
leukocyte count < 5000 cells/mm3,I/T ratio > 0.2, ANC
(Absolute Neutrophil Count) < 1800 cells/mm3, micro-ESR
>15 mm at the end of 1st hour, C reactive protein> 1
mg/dl. If any two of the following parameters are positive or
significant, the sepsis screen is said to be positive as per NNF
guidelines

All the study parameters were entered in the excel sheet and were
analysed using epi-info software. Descriptive parameters were used for
the univariate analysis. Sensitivity, specificity, Negative Predictive
Value (NPV) and Positive Predictive Value (PPV) of septic screen was
compared with culture outcome (gold standard) using a contingency table.

Results

The general characteristics of study population are shown in table 1.
Total 200 newborns were included in the study out of which 64.5% were
outborns and 35.5% were inborns. 47% had early onset sepsis, while 53%
had late onset sepsis. There were 62% male and 38% female. The ratio of
male to female is nearly 1.6:1. 8.5% were less than 32 weeks gestation,
45% between 32 to 37 weeks and 46.5% more than 37 weeks. 33.5% were
VLBW, 41.5% LBW and 25% had a birth weight of more than 2.5 kg.

Table-1: General study
population characteristics

Gender

Males

62%

Females

38%

Gestational age

<32 weeks

8.5%

32-37weeks

45%

>37 weeks

46.5%

Place of birth

Inborn

35.5%

Outborn

64.5%

Birth weight

<1.5kg

33.5%

1.5 to 2.5kg

41.5%

>2.5kg

25%

Onset of sepsis

EOS

47%

LOS

53%

The newborns were included if they had the signs and symptoms of
probable sepsis according to the NNF criteria. Table 2 shows the
distribution of various major presenting complaint. Respiratory
distress was the most common major presentation found in 56% of
patients.

Table-2: Distribution of
cases according to clinical presentation

Number

Percent

Abdominal Distention

2

1

Aponea

8

4.0

Dullness

39

19.5

Hypothermia

3

1.5

Jaundice

10

5.0

Respiratory distress

112

56.0

Refusal to feed

21

10.5

Seizures

5

2.5

Total

200

100.0

Out of the 200 patients with suspected sepsis, 150 (75%) had a positive
sepsis screen whereas 102 (51%) were culture positive. Table 2 The most
common organism isolated was Klebsiella pneumoniae in 18.5% cases
followed by 15.5% of staphylococcus aureus& 8.5% of E-Coli,
4.5% of Enterococcus, 3.5% of Pseudomonas, & 0.5% of
Citrobacter.

The above table shows that Sepsis Screen was positive in 93.1% of total
culture positive sepsis and negative in 6.9%. It was positive in 56.1%
of culture negative cases too. Thus, the Sensitivity and specificity
for Septic Screen was calculated to be 93.18 and 43.88% repetitively.
PPV was 63.33% and NPV was 86.0 %.

The individual parameters of the sepsis screen were also assessed for
their strength of prediction of sepsis. Table 4 shows the values of
specificity, sensitivity, PPV and NPV for the different parameters.

Table 4: Table showing
values of specificity, sensitivity, PPV and NPV for the different
parameters

Parameter

Sensitivity

Specificity

PPV

NPV

Micro-ESR

48.02

73.47

65.33

57.60

CRP

87.25

45.92

62.68

77.59

I/T ratio

80.39

49.98

62.12

70.59

Platelet count

91.18

35.71

59.62

79.55

Leukopenia

52.54

52.26

64.58

42.86

Positive M-ESR was seen in 48% of total sepsis cases in positive
culture and 26.5% in culture negative cases including both inborn and
outborn. Sensitivity and specificity for M-ESR was 48.04 and 73.47%
repetitively. PPV was 65.33 % and NPV was 57.60%

Positive CRP was seen in 87.3% of total sepsis cases in positive
culture and 54.1% in culture negative cases including both inborn and
outborn. Sensitivity and specificity for CRP was 87.25 and 45.92%
repetitively. PPV was 62.68 % and NPV was 77.59 %

Positive I/T ratio was seen in 57.8% of total sepsis cases in positive
culture and 58.2% in culture negative cases including both inborn and
outborn. Sensitivity and specificity for I/T ratio was 80.39 and 49.98%
repetitively. PPV was 62.2 % and NPV was 70.59%

Thrombocytopenia was seen in 91.2% of total sepsis cases in positive
culture and 87.8% in culture negative cases including both inborn and
outborn. Sensitivity and specificity for Thrombocytopenia was 91.18 and
35.71% repetitively. PPV was 59.62 % and NPV was 79.55 %

Leucopenia was seen in 56.9% of total sepsis cases in positive culture
and 65.3% in culture negative cases including both inborn and out born.
Sensitivity and specificity for Leukopenia was 52.54 and 52.26%
repetitively. PPV was 64.58 % and NPV was 42.86%

Discussion

Blood culture has remained the gold standard for the confirmation of
sepsis. In our study, 51% neonates with suspected sepsis had positive
cultures. Other authors have observed culture positivity in 30 to 55%
patients in different studies [8-10]. At advanced centres, blood
culture is positive in upto 80% of genuine sepsis [11]. Thus culture
positivity rate is highly variable from place to place.

The most common organism isolated in present study was Klebsiella
pneumoniae followed by staphylococcus aureusfollowed by E.Coli. This
finding is in accordance with NNPD 2002 – 03 data, where the
most common organisms causing neonatal sepsis was Klebsiella pneumoniae
followed by staphylococcus aureus and pseudomonas [12]. However other
studies have reported Staphylococcus aureus as the commonest organism
to be isolated [13].

In our study, when comparing early onset and late onset sepsis, we
found that Klebsiella pneumoniae was the most common isolate in early
onset sepsis while in late onset sepsis it was Staphylococcus aureus.
While in the developed world Group BStreptococcus is the commonest
organism responsible for Early onset sepsis which is quite in contrast
to the developing world [14].

In our study, both Gram-positive and Gram-negative isolates showed a
high resistance to cephalosporins, penicillin, gentamycin and
amoxiclav. Thakur et al observed that antibiotic resistance among the
Gram-positive isolates was highest to penicillin (87%) followed by
amoxyclav (66%)[15]. Reports of high resistance to Ampicillin (71%) has
also been reported by Bhat et al [16]. In the current study most of the
Gram-positive isolates were sensitive to vancomycin which is also seen
in the study by Hoogen et al [17].

Gram-negative isolates showed a high resistance to all cephalosporins
which is like the resistance pattern reported by Agnihotri et al[18]
and Bhat et al[16,18].This high resistance pattern could be attributed
to the injudicious use of antibiotics in our region.

In a study conducted by Dr Zafar Khan 2003 in our NICU, it was found
that E Coli was the commonest organism isolated in newborns with sepsis
followed by Klebsiella pneumoniae. That time the isolated E coli was
mostly susceptible to ciprofloxacin and Klebsiella isolates were
sensitive to amikacin. But in the present scenario both the organisms
are resistant to quinolones as well as aminoglycosides and only
sensitive to meropenem and colistin. This shows that bacteriological
profile and the sensitivity pattern has changed over a period and the
organisms have gained resistance to the first and second line therapy.

In the present study, overall mortality was observed in 29%, whereas
Chaudhary reported a mortality of 45.5% in their study, which is quite
high as compared to our study. Thakur et al also reported the low
mortality rate (11.7%). This could be attributed to advancement in
medical technology and better neonatal care in NICU.

Two or more abnormal parameters of the sepsis screen had a high
accuracy in predicting neonatal sepsis. While comparing the validity of
sepsis screen results between various studies, a lot of variation has
been noticed. The table below compares the values among various studies.

Table 5: Comparison of
sepsis screen validity in different studies

No.

Authors

Year

Sensitivity
(%)

Specificity
(%)

Positive
predictive value (%)

Negative
predictive value (%)

1

Gerdes et al.

2004

100.0

83.0

27.00

100.0

2

Sriram et al.

2011

55.30

91.70

98.30

19.30

3

Swarnakar et al.

2012

56.0

87.50

97.00

20.00

4

Jadhav et al.

2013

100.0

62.50

63.30

100.0

5

Vinay et al,

2015

77

41

84

31

6

Bhale et al.

2015

93.4

77.0

78.7

92.77

7.

Present Study

2016

93.18

43.88

63.33

86.0

Some studies have reports very high sensitivities and negative
predictive value up to 100% while some reported very high specificities
and positive predive value upto 92 to 97 % [19-24]. Our study found a
high sensitivity and NPV of the sepsis screen of 93.18% and 86%
respectively whereas slightly lower specificity and PPV of 43.88% and
63.33% respectively. The sensitivity results in the present study were
in accordance with Gerdes et al, Jadhav et al., and Bhale et al
[19,22,24].

When comparing the individual parameters of sepsis screen, platelet
count was found to be the most sensitive indicator of sepsis followed
by CRP and I/T ratio in order. And micro ESR was found to be the most
specific indicator of sepsis.

Thesensitivity, Specificity, PPV and NPV of the platelet count as an
individual parameter were very comparable to the full sepsis screen.

Conclusion

The organisms causing sepsis have changed over time, with Klebsiella
now being the most common as compared to E.Coli earlier (2003 study).
Also, there is a marked prevalence of antibiotic resistance among the
prevalent organisms.

The sepsis screen is quick and is helpful in differentiating possible
sepsis from probable sepsis. As sepsis screen has a high Negative
Predictive Value, its main value remains in excluding the infections
rather than confirming sepsis. If the sepsis screen is negative in the
presence of strong clinical suspicion, it should be repeated within 12
hours. If the screen is still negative, sepsis can be excluded with
reasonable certainty.

Excluding sepsis with sepsis screen will make possible more rationale
use of antibiotics and limit the empirical use. This will prevent
development of resistance as well as save money spent on neonatal care.

We studied the individual parameter of septic screen and found that
platelet count is the most sensitive predictor of sepsis followed by
CRP. Thus, if a neonate has a normal platelet count and CRP, sepsis can
be quite reasonably excluded.

Normal platelet count and normal CRP can reasonably assure us to
withhold antibiotics. Limiting antibiotics overuse is of utmost
importance in a NICU.

As platelet count has near comparable Sensitivity, Specificity, PPV and
NPV as the full sepsis screen, other studies which may include a higher
number of newborns may be conducted to see whether thrombocytopenia
alone along with the clinical signs of sepsis is good enough to call it
as probable sepsis instead of the full screen. This might be useful in
resource poor settings.

We also recommend yearly or time to time analysis of sepsis in all
nurseries with their bacteriological profile and their sensitivity
pattern, which will help to prevent antibiotic resistance.

What this study adds?
1. The NPV and sensitivity of sepsis
screen is very high so its main use should in excluding infection
rather than confirming it.
2. Drug resistant strains of Klebsiella
pneumoniae is the most common organism in present situation.
3. Normal platelet count can be very
helpful and reassuring especially in resource poor settings to exclude
sepsis.